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Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease
Nakamura K, Greenwood A, Binder L, Bigio EH, Denial S, Nicholson L, Zhou XZ, Lu KP.. Cell, 2012-03-01
Topic: Amyloid, tau and blood-test diagnosis
cis-trans isomerization of proteins phosphorylated by proline-directed kinases is proposed to control numerous signaling molecules and is implicated in the pathogenesis of Alzheimer's and other diseases. However, there is no direct evidence for the existence of cis-trans protein isomers in vivo or for their conformation-specific function or regulation. Here we develop peptide chemistries that allow the generation of cis- and trans-specific antibodies and use them to raise antibodies specific for isomers of phosphorylated tau. cis, but not trans, p-tau appears early in the brains of humans with mild cognitive impairment, accumulates exclusively in degenerated neurons, and localizes to dystrophic neurites during Alzheimer's progression. Unlike trans p-tau, the cis isomer cannot promote microtubule assembly, is more resistant to dephosphorylation and degradation, and is more prone to aggregation. Pin1 converts cis to trans p-tau to prevent Alzheimer's tau pathology. Isomer-specific antibodies and vaccines may therefore have value for the early diagnosis and treatment of Alzheimer's disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nakamura, K., Greenwood, A., Binder, L., Bigio, E. H., Denial, S., Nicholson, L., et al. (2012). Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease. Cell. https://doi.org/10.1016/j.cell.2012.02.016
Vancouver
Nakamura K, Greenwood A, Binder L, Bigio EH, Denial S, Nicholson L, et al. Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease. Cell. 2012. doi:10.1016/j.cell.2012.02.016. PMID: 22464332.
BibTeX
@article{nakamura2012-22464332,
author = {Nakamura, K. and Greenwood, A. and Binder, L. and Bigio, E. H. and Denial, S. and Nicholson, L. and Zhou, X. Z. and Lu, K. P.},
title = {{Proline isomer-specific antibodies reveal the early pathogenic tau conformation in Alzheimer's disease}},
journal = {Cell},
year = {2012},
doi = {10.1016/j.cell.2012.02.016},
pmid = {22464332},
url = {https://doi.org/10.1016/j.cell.2012.02.016}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- However, there is no direct evidence for the existence of cis-trans protein isomers in vivo or for their conformation-specific function or regulation.
- Here we develop peptide chemistries that allow the generation of cis- and trans-specific antibodies and use them to raise antibodies specific for isomers of phosphorylated tau. cis, but not trans, p-tau appears early in the brains of humans with mild cognitive impairment, accumulates exclusively in degenerated neurons, and localizes to dystrophic neurites during Alzheimer's progression.
- Unlike trans p-tau, the cis isomer cannot promote microtubule assembly, is more resistant to dephosphorylation and degradation, and is more prone to aggregation.
- Pin1 converts cis to trans p-tau to prevent Alzheimer's tau pathology.
- Isomer-specific antibodies and vaccines may therefore have value for the early diagnosis and treatment of Alzheimer's disease.
Why it matters
Antibodies that distinguish cis from trans forms of phosphorylated tau showed that the cis form appears early in the brains of people with mild cognitive impairment and accumulates in degenerated neurons. Unlike trans p-tau, the cis isomer cannot promote microtubule assembly and is more prone to aggregation, and the authors suggest isomer-specific antibodies or vaccines may have value for early diagnosis and treatment.
Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell) |
| Journal's citation record | 4 / 4 | Cell: journal h-index 1,220 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 257 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 11.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kun Ping Lu: h-index 83 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22464332) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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